The Pharmacology of an Iron‐dextran Intramuscular Haematinic

Abstract

An iron preparation suitable for intramuscular injection should conform to the following criteria: (a) it should be rapidly absorbed from the muscle and the total iron content should be available for haemoglobin synthesis, (b) in order to avoid pain, the pH and tonicity should approximate to those of normal tissue fluids, (c) it should be stable in the presence of protein and electrolytes, (d) it should possess a low toxicity, and be stable on storage, (e) in order to keep the injection volume down to a minimum, the solution should contain at least 5% w/v of iron.Previous workers have described the subcutaneous or intramuscular administration of compounds containing either ionic iron (Brownlee, 1942; Goldberg and Hutchison, 1953) colloidal ferric hydroxide, or saccharated oxide of iron (Slack, 1949), but preparations which contained sufficient iron to be useful in the treatment of hypochromic anaemia were found to be either toxic or painful.Initially, we investigated two series of iron compounds. In the first series, the iron was present as a co-ordination compound, e.g., ferrous calcium ethylenediaminetetraacetate, and other ferrous or ferric alkali, alkaline earth, or organic base salts of ethylenediaminetetraacetic acid. In the second series, the preparations were based on saccharated oxide of iron, but other sugars were used in place of sucrose. On investigation in animals, compounds of the first series caused systemic haemorrhage and were rejected; none of the preparations in the second series showed satisfactory absorption from muscle, and some were, in addition, very toxic.Iron is stored in the body as a macromolecular protein complex, ferritin, and is also transported in combination with the protein, al-globulin. It was decided, therefore, to investigate the substitution of the protein moiety by other macromolecules; a third series was therefore investigated in which the 2C

Iron overload inhibits late stage autophagic flux leading to insulin resistance

“…As in previous studies which have adopted injections to induce IO [48,49], we delivered iron intravenously at 15 mg/kg, a dose with minimal toxicity [50], via three injections at 2-h intervals (Fig 6A). Twenty-four hours after first administration, animals were sacrificed, and tissue iron accumulation examined with Perls Prussian Blue Staining.…”

The Cellular Transformation of Injected Colloidal Iron Complexes Into Ferritin and Hemosiderin in Experimental Animals

“…Such a separation is necessary if ferric hydroxide contained in iron-dextran is to precipitate out within cells and to form large aggregates; for colloidal iron-dextran is quite stable over a wide pH range (31). The closely packed aggregates of particles and "filaments" seen in electron micrographs are visible under the light microscope as brown granules (i.e.…”

Lymph node iron in rheumatoid arthritis. Histology, ultrastructure, and chemical concentration.

“…(Karlefors and Norden, 1958). From the circulation iron dextran, which has a molecular weight of 180,000 to 230,000, is extracted by the RES before being utilized for red cell production (Martin, Bates, Beresford, Donaldson, McDonald, Dunlop, Sheard, London, and Twigg, 1955), and even iron sorbitol, with a low molecular weight of less than 5,000, is metabolized in part at least through the RES (Wetherley-Mein, Buchanan, Glass, and Pearce, 1962). Ferritin is found when iron dextran is taken up by subcutaneous macrophages (Muir and Golberg, 1961) and by synovial cells (Ball, Chapman, and Muirden, 1964), and there seems to be no reason why phagocytic reticulum cells of lymph nodes should not be capable of this conversion.…”